Investigation of teratogenic mechanism will be intensified. Major effort will be concentrated on connecting drug-induced biochemical or morphological changes with specific embryonic events which are interfered with in the pathogenesis of a particular malformation. The basis of physiological necrosis in the preaxial limb bud mesoderm will be examined and its prevention by drugs which induce polydactyly studies. The biochemical, genetic and embryological basis of sensitivity to acetazolamide teratogenesis will be explored in two mouse strains, one sensitive and one resistant to the teratogenic effects of this carbonic anhydrase inhibitor. Nucleotide metabolism and control in rat embryos and their perturbation by teratogenic antiproliferative agents constitute another segment of proposed studies. These investigations represent the underlying thought that only by intense biochemical and morphological examination of specific teratogenic situations can we further understand how development can be disturbed sufficiently to result in birth defects.